Identification of Pediatric Brain Neoplasms Using Raman Spectroscopy

Abstract

Purpose: Raman spectroscopy can quickly and accurately diagnose tissue in near real-time. This study evaluated the capacity of Raman spectroscopy to diagnose pediatric brain tumors. Experimental Design: Samples of untreated pediatric medulloblastoma (4 samples and 4 patients), glioma (i.e. astrocytoma, oligodendroglioma, ependymoma, ganglioglioma and other gliomas; 27 samples and 19 patients), and normal brain samples (33 samples and 5 patients) were collected fresh from the operating room or from our frozen tumor bank. Samples were divided and tested using routine pathology and Raman spectroscopy. Twelve Raman spectra were collected per sample. Support vector machine analysis was used to classify spectra using the pathology diagnosis as the gold standard. Results: Normal brain (321 spectra), glioma (246 spectra) and medulloblastoma (82 spectra) were identified with 96.9, 96.7 and 93.9% accuracy, respectively, when compared with each other. High-grade ependymomas (41 spectra) were differentiated from low-grade ependymomas (25 spectra) with 100% sensitivity and 96.0% specificity. Normal brain tissue was distinguished from low-grade glioma (118 spectra) with 91.5% sensitivity and 97.8% specificity. For these analyses, the tissue-level classification was determined to be 100% accurate. Conclusion: These results suggest Raman spectroscopy can accurately distinguish pediatric brain neoplasms from normal brain tissue, similar tumor types from each other and high-grade from low-grade tumors.

Accuracy of Raman spectroscopy in differentiating brain tumor from normal brain tissue

“…Four studies [17, 18, 24, 26] examined glioma. The pooled sensitivity and specificity of Raman spectroscopy for discriminating glioma and normal brain tissues were 0.96 (95% CI 0.94-0.97) and 0.99 (95% CI 0.98-0.99), respectively.…”

“…Third, Raman spectroscopy causes no harm to the patients, which differs from the traditional biopsy [29]. Besides, the high accuracy of Raman decreases the number of expensive tests, such as immunohistochemical staining, fluorescent in situ hybridization, electron microscopy or karyotyping, which are prescribed to guarantee the correct diagnosis [26]. Furthermore, the handheld Raman probe is small and easy to use during the surgery [30].…”

“…Furthermore, the handheld Raman probe is small and easy to use during the surgery [30]. Raman spectroscopy can both quickly and effectively detect and analyze brain tissue in vivo as well as providing accurate tumor margin assessment by rapidly scanning [26]. With clear knowledge of margin, it contributes to avoid removal of normal tissue and to minimize the volume of residual tumor which poses a considerable impact on patient survival [24].…”

Raman spectroscopy as a promising noninvasive tool in brain cancer detection

“…Spectra from normal brain (n ¼ 321), glioma (n ¼ 246), and medulloblastoma (n ¼ 82) showed an accuracy of 96.9%, 96.7%, and 93.9%, respectively. 30 Meningioma, glioma, and brain metastasis (from 15 patients each) were distinguished with respect to normal brain samples (n ¼ 7) by Gajjar et al who used both FTIR and RS to achieve the goal. 31 In the recent years, di®erent types of brain tumors have been explored by several groups, including Aguiar et al (tumors: glioblastoma, medulloblastoma, and meningioma; normal:cerebellum and meninges), 32 Beleites et al (astrocytoma), 33 Kalkanis et al (normal brain, glioblastoma multiforme, and necrosis), 34 Kast et al (normal brain, necrosis, di®usely in¯ltrating glioma and solid glioblastoma), 35 Kast et al (boundaries of normal gray and white matter, glioblastoma and necrosis).…”

Towards real-time optical brain biopsies?

“…However, it would have been of major interest to confirm the interrater concordance of TPEF-CARS image interpretation by several pathologists blinded to the H&E images. Moreover, the accuracy of real-time automatic classification of brain tumours is often claimed [9] but should be confirmed in larger cohorts of unsupervised brain pathologies, and at least in pristine pieces of brain resection, while waiting for possible future neurosurgical implementation.…”